Exercise Hippocampus and their role in Stress Neeraj

Exercise, Hippocampus and their role in Stress Neeraj Kumar Tiwari 10 -20 -2017

Treadmill exercise can rescue social defeat-induced anxiety-like behavior G. Patki et al. / Physiology & Behavior 130 (2014) 135– 144

Exercise and Stress affect the endocannabinoid system and GABAergic neurons in the hippocampus Stress Exercise Hippocampus Endocannabinoid system GABAergic neurons

Endocannabinoid system https: //www. sclabs. com/the-endocannabinoid-system-and-stress-related-psychiatric-illness/

Endocannabinoids https: //www. sclabs. com/the-endocannabinoid-system-and-stress-related-psychiatric-illness/

Endocannabinoid receptors https: //en. wikipedia. org/wiki/Cannabinoid_receptor#

Overexpression of CB 2 cannabinoid receptors decreased vulnerability to anxiety and impaired anxiolytic action of alprazolam in mice Marı´a S Garcı´a-Gutie´rrez and Jorge Manzanares Journal of Psychopharmacology, 2011 25(1) 111– 120

Open Field Test http: //biomed. au. dk/fileadmin/_migrated/pics/Open_field_SG. png

Cb 2 gene overexpression leads to increase time spent in the center during open field test

Light-dark Box test https: //image. slidesharecdn. com/screeningofanxiolytic-150210221920 -conversion-gate 02/95/screening-of-anxiolytics

Cb 2 gene overexpression leads to increase time spent in the light during light-dark box test

Elevated plus maze test http: //www. cidd. unc. edu/images/elevated. Plus. Maze. jpg

Cb 2 gene overexpression leads to increase time spent in the open arm at elevated plus maze test

Alprazolam treatment increase time spent in the light during light-dark box test

Alprazolam treatment has no effect on Cb 2 overexpressing mice during light-dark box test

Increased expression of GABA receptors in Cb 2 overexpressing mice

Summary: • Cb 2 receptor overexpression has anxiolytic effects as it is evident from the open field test, light-dark box test and elevated plus maze test. • Cb 2 receptor overexpression leads to increase in expression of GABAA receptors in hippocampus.

Different role of dorsal and ventral hippocampus B. R. 152 Levone et al. / Neurobiology of Stress 1 (2015) 147 e 155

ANXIOUS BEHAVIOR INDUCES ELEVATED HIPPOCAMPAL Cb 2 RECEPTOR GENE EXPRESSION JAMES M. ROBERTSON, JUSTIN K. ACHUA, JUSTIN P. SMITH, MELISSA A. PRINCE, CLARISSA D. STATON, PATRICK J. RONAN, TANGI R. SUMMERS AND CLIFF H. SUMMERS Neuroscience 352 (2017) 273– 284

Stress-Alternatives Model (SAM)

Freezing Time increased in submissive mice

Escape latency decreased in escaping mice

No effect on Cb 1 receptor expression in ventral dentate gyrus and ventral CA 1 region of hippocampus

Cb 2 receptor expression in ventral dentate gyrus and ventral CA 1 region of hippocampus increased

No effect on Cb 1 receptor expression in dorsal dentate gyrus and dorsal CA 1 region of hippocampus

Cb 2 receptor expression in dorsal dentate gyrus and dorsal CA 1 region of hippocampus increased

Exercise has no effect on Cb 1 expression in ventral dentate gyrus region of mice which went through SAM social aggression

Exercise has no effect on Cb 2 expression in ventral dentate gyrus and ventral CA 1 region of mice which went through SAM social aggression

Exercise caused increased Cb 2 expression in dorsal dentate gyrus but not dorsal CA 1 region of mice which went through SAM social aggression

Summary: • There is increased expression of Cb 2 receptors in ventral and dorsal dentate gyrus region of hippocampus in submissive mice which went through social defeat. • Running and Social defeat stress leads to increased expression of Cb 2 receptors in dorsal dentate gyrus region of hippocampus in mice showing escape and submissive behavior.

Physical Exercise Prevents Stress-Induced Activation of Granule Neurons and Enhances Local Inhibitory Mechanisms in the Dentate Gyrus Timothy J. Schoenfeld, Pedro Rada, Pedro R. Pieruzzini, Brian Hsueh, and Elizabeth Gould The Journal of Neuroscience, May 1, 2013 • 33(18): 7770 – 7777

Running increased the number of newly formed neurons in the dentate gyrus of hippocampus

Running prevents activation of new neurons in the ventral dentate gyrus due to stress

Running prevents activation of granule neurons in ventral dentate gyrus due to stress

Interneurons in the ventral dentate gyrus shows increased activity to stress in runners as compared to sedentary mice

Microdialysis https: //www. researchgate. net/profile/Hartmut_Derendorf/publication/6369883/figure/fig 1

There was increase in extracellular GABA in ventral hippocampus in runners due to stress as compared to sedentary mice

Increase in GABA receptor staining in ventral hippocampus in runners as compared to sedentary mice

GABA receptor antagonist Bicuculline when administered in ventral hippocampus caused decrease in time spent in open arms by the runners

Bicuculline doesn't cause any effect if the treatment was given in dorsal hippocampus in runners

Summary: • There was increase in extracellular GABA in ventral hippocampus in runners due to stress as compared to sedentary mice. • Increase in GABA receptor staining in ventral hippocampus in runners as compared to sedentary mice.

Conclusion

Endocannabinoid binding to the presynaptic site can lead to release of GABA http: //www. neurology. org/content/69/3/306/F 1. large. jpg

GABAergic signaling in the hippocampus Ge et. al, (2007)TRENDS in Neurosciences Vol. 30 No. 1

Exercise and Stress affect the endocannabinoid system and GABAergic neurons in the hippocampus Exercise Hippocampus Endocannabinoid system GABAergic signaling Reduces the excitatory signals created due to Stress